Cancer combat is a great challenge for human beings this end, cancer chemotherapeutic drugs have been vigorously developed, but no drugs that have cancer cell-specific effects have been created yet. Angiogenesis in cancer is essential for growth and metastasis of solid cancer. The development of angiogenesis inhibitors for cancer therapy is different in direction from the conventional anticancer drug development based on direct actions on cancer cells. Angiogenesis inhibitors for cancer affect the unique microenvironment surrounding tumor cells, and therefore are expected to reduce the development of drug-resistant cancer cells and to enhance the specificity of effects on cancer cells. Based on such a concept, the following drugs have been created: bevacizumab (trade name: Avastin), a monoclonal antibody inhibiting the binding of a proangiogenic factor VEGF (vascular endothelial growth factor) to its receptor; and sorafenib (trade name: Nexavar) and sunitinib (trade name: Sutent), which inhibit tyrosine kinase receptors including VEGF receptor. These three drugs are clinically used, but have problems in terms of limited indication, side effects, etc. Further, considering that all these drugs have the same action mechanism relevant to inhibition of VEGF signal transduction, it is a quite crucial issue to create novel pharmaceuticals which are different in chemical structure and action mechanism from these drugs.
Under such circumstances, the present inventors focused on vascular endothelial cells, a key player in cancer angiogenesis, and screened for natural substances having selective anti-proliferative activity against vascular endothelial cells. As a result, the present inventors found that the methanol extract from Corticium simplex, an Indonesian marine sponge, has specific anti-proliferative activity against human umbilical vein endothelial cells (HUVEC). Then, with the guidance of bioassay, the present inventors purified active substances from the methanol extract, analyzed their chemical structures, identified four kinds of novel modified steroidal alkaloids having an oxabicyclo[3.2.1]octene moiety and an isoquinoline side-chain, and named these steroidal alkaloids as cortistatins. The present inventors confirmed that, in particular, cortistatin A, which is represented by the formula below, shows more than 3000 times stronger anti-proliferative activity against HUVEC (IC50=1.8 nM) than against other cancer cells, and inhibits the migration and tubulogenesis of HUVEC, which are regarded as essential indicators of angiogenesis; and in addition, demonstrated that the mechanism of such actions is not relevant to inhibition of VEGF signal transduction (see Non Patent Literature 1 to 3).

However, cortistatins can be obtained in only very small amounts from natural sources, and the industrial production of cortistatins by chemical synthesis is difficult cue to their complicated chemical structures. Therefore, novel cortistatin analogs which can be mass-produced are desired.
Known analogs of cortistatin A include, for example, those described in Patent Literature 1 to 3. However, these analogs have a chemical structure as complicated as that of cortistatin A and require multiple steps for synthesis, and thus are not suitable for industrial mass-production.